Colorectal cancer is the second leading cause of cancer death in the United States. In 1996, approximately 133,500 new cases will occur and approximately 55,000 persons will die from this disease. Several studies have shown that screening asymptomatic populations for colorectal neoplasia can reduce mortality. Molecular genetic studies have demonstrated that the mutational activation of ras proto-oncogenes and mutational inactivation of tumor suppressor genes are associated with colorectal tumorigenesis. The objective of this proposal is to explore genetic approaches for early detection of colorectal cancer. We seek to achieve the following: 1. Generate a robust method for detecting ras gene mutations in stool specimens in an effort to provide a single specimen screening test for colorectal cancer. Evaluate test sensitivity and specificity through retrospective analysis of stool samples previously obtained from subjects with documented carcinomas or adenomas. 2. Compare the genetic method for detecting fecal ras oncogene mutation with an immunochemical test for fecal occult blood in a prospective study in patients undergoing surveillance colonoscopy.